HCID 12841581, compound → HCID 178499062, compound

Participants

Reaction Steps

To a mixture of acetic acid/hydrochloric acid (1:1, 20 mL) at 0° C. was added methyl 3-amino-6-phenylpyrazine-2-carboxylate (1.02 g, 4.50 mmol). Aqueous solution of sodium nitrite (0.77 g, 11.2 mmol) was added drop wise. During the addition, the temperature of the reaction was controlled at 0-5° C. The reaction was slowly warmed to room temperature and stirred overnight. The reaction mixture was extracted with ethyl acetate (2×50 mL). The organic layer was washed with water (30 mL), saturated aqueous sodium chloride (30 mL), dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford the crude methyl 3-hydroxy-6-phenylpyrazine-2-carboxylate which was used in the next step with out any purification. The crude product was treated with phosphorus oxychloride (30 mL) and heated to 90° C. for 2 h. The reaction was cooled to room temperature and poured into ice-water mixture and extracted with ethyl acetate (3×40 mL). The organic layer was washed with water (30 mL), saturated aqueous sodium chloride (30 mL), dried over magnesium sulfate, filtered, and concentrated to give crude product. Column purification on silica (8:2 hexanes/ethyl acetate) afforded methyl 3-chloro-6-phenylpyrazine-2-carboxylate (0.22 g, 20% yield) as yellow solid: 1H NMR (400 MHz, CDCl3): δ 8.90 (s, 1H), 8.02 (t, 2H), 7.40 (t, 1H), 7.20 (br s, 2H), 3.90 (s, 3H): MS (EI) for C12H9N2O2Cl: 249 (MH+).

Provenance & Evidence